ARF Essay - 748 Words

Decreased expression of ARF in human cancer Consistent with the findings in mice, frequent mutation or deletion of the ARF/INK4a in numerous human cancers was discovered (Refs. 41, 68, 69; Table 1). It is difficult, however, to assess the relative importance of p16INK4a and p14ARF individually in humans since mutation or deletion at the ARF/INK4a locus frequently affects both proteins (Ref. 8). Generally, exon 2 is the site of mutation, affecting either p16INK4a, p14ARF, or both proteins. Some of these exon 2 mutations alter ARF localization and affect its regulation of downstream target proteins (Refs. 71, 72). Silencing of the ARF gene promoter through hypermethylation is frequently observed in human cancers (Ref. 73) although the†¦show more content†¦78), which had been proved in a mouse model (Ref. 6). ARF overexpression in human cancer Silva et al. (Ref. 83) have performed a comprehensive analysis of the inactivation mechanisms (mutation, homozygous and hemizygous deletion, and promoter hypermethylation) in of 100 primary breast carcinomas. RT-PCR showed expression variable of the p14ARF transcript, with 17% overexpression and 26% decreased expression. No detectable alterations were observed in the majority of cases with overexpressed p14ARF mRNA, but 77% of tumors with decreased expression showed one or more of these genetic alterations (Ref. 83). A significant correlation was observed between decreased p14ARF expression and poor prognostic parameters. The same group later studied the inactivation mechanisms that alter the levels (Ref. 84). Furthermore, the interdependence of inactivation mechanisms was studied since it had been reported that p14ARF was altered in tumors in concordance with p16INK4a. They showed that promoter hypermethylation was the major mechanism of inactivation of these genes, which was present in 31% and 50% of the tumors that showed decreased p16INK4a and p14ARF expression, respectively. No detectable inactivation mechanisms were observed in tumors overexpressing p16INK4a or p14ARF. In conclusion, these tumor suppressor proteins were often co-altered in human breastShow MoreRelatedArf Case Study Essay2506 Words   |  11 PagesARF Case Study Acute Renal Failure Case Study Directions: Please carefully read the following case study and answer the following questions in typed format. The resources that you will need to complete this case study include your textbook and drug book. Please include in text citations. This independent assignment is worth 25 points. Ann Hayes, age 68, initially was admitted to the hospital for elective surgical repair of an abdominal aortic aneurysm. 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